NEURAL BASIS OF DRUG CRAVING

药物渴望的神经基础

• 批准号: 2120951
• 负责人: Kent C. Berridge
• 金额: $ 4.27万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2120951
• 关键词: amphetamines; behavior test; chemical stimulation; cocaine; discrimination learning; drug addiction; drug administration rate /duration; drug interactions; drug withdrawal; laboratory rat; model design /development; neuropharmacology; operant conditionings; pleasure; psychological models; psychopharmacology; reinforcer; relapse /recurrence; taste; videotape /videodisc

APPLICANT'S ABSTRACT: This application addresses two questions: 1. What is the psychological and neurobiological basis of drug craving, and 2. Why can drug craving persist so long after drug use (and withdrawal) has ended? These questions are posed in light of a new theory of drug addiction, The Incentive-Sensitization Theory (Robinson & Berridge, 1993). The theory posits that the repeated use of drugs such as cocaine or amphetamine sensitizes ventral striatal dopamine systems, rendering them perhaps permanently hypersensitive. The theory also posits that sensitized dopamine systems mediate a psychological process, the attribution of incentive salience, which transforms the perception of stimuli into subjective incentives that are attractive and "wanted". Sensitization of this dopamine system results in excessive incentive salience being attributed specifically (by associative learning) to drug-related stimuli. This leads in addiction to the subjective experience of excessive wanting or "craving". Further, the theory posits that these dopamine systems of drug craving are completely independent of systems that mediate both the subjective pleasurable effects of drugs and the subjective aversive effects of withdrawal. Thus, sensitization of these systems produces obsessive drug craving and compulsive drug-seeking behavior even if the drug is not expected to produce pleasure and even in the absence of subjective withdrawal symptoms. The incentive-sensitization theory of addiction makes specific testable predictions about the relation between "wanting" and "liking" drugs. Experiments are proposed here to test these predictions. For example, the theory predicts that repeated exposure to drugs will increase only the incentive effects of drug-related stimuli ("wanting") in the absence of an increase in hedonics ("liking"). A behavioral method will be developed to directly study the relation between "wanting" and "liking", and to determine if sensitization by cocaine or amphetamine can enhance instrumental behavioral measures of "wanting" without enhancing behavioral "affective reactivity" measures of "liking". These studies will provide a strong test of the incentive-sensitization theory. The truth of the theory is directly relevant to the clinical treatment of drug addiction because, if it is true, the theory makes novel predictions about the nature of medications that would effectively treat drug craving.

申请人的摘要：此申请解决了两个问题：1。 是渴望药物的心理和神经生物学基础，以及2。 毒品渴望在吸毒（和戒断）结束后能否持续很长时间？ 这些问题是根据一种新的药物成瘾理论提出的 激励敏化理论（Robinson＆Berridge，1993）。 理论 假定重复使用可卡因或苯丙胺等药物 使腹侧纹状体多巴胺系统敏感，也许使它们 永久性高度敏感。 该理论还认为这一点敏感 多巴胺系统介导心理过程 激励显着性，这将刺激的感知转化为 具有吸引力和“想要”的主观激励措​​施。 灵敏度 这种多巴胺系统导致过多的激励显着性 专门归因于与药物相关的刺激。 这导致了过度渴望的主观经历 或“渴望”。 此外，该理论认为这些多巴胺系统 渴望药物完全独立于介导的系统 药物的主观愉悦作用和主观厌恶效果 退出。 因此，这些系统的敏化产生了痴迷 渴望和强迫毒品的毒品行为，即使该药物不是药物 期望产生快乐，甚至在没有主观的情况下 戒断症状。 成瘾的激励敏感理论使特定可检验 关于“想要”和“喜欢”药物之间关系的预测。 这里提出了实验来测试这些预测。 例如， 理论预测，反复接触药物只会增加 在没有药物相关刺激的激励效果（“想要”）的情况下 享乐者的增加（“喜欢”）。 将开发一种行为方法 直接研究“想要”和“喜欢”之间的关系，与 确定可卡因或苯丙胺的敏化是否可以增强 “想要”的工具行为度量而不增强行为 “喜欢”的“情感反应性”度量。 这些研究将提供 激励敏感理论的强烈检验。 理论的真理 与药物成瘾的临床治疗直接相关，因为 如果是真的，那么该理论就会对 可以有效治疗药物渴望的药物。